Title:Targeting Drug-Resistant Prostate Cancer with Dual PI3K/mTOR Inhibition
Volume: 21
Issue: 26
Author(s): K.D. Tang and Ming-Tat Ling
Affiliation:
Keywords:
Drug resistant, PI3K, mTOR, prostate cancer.
Abstract: The phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR pathway is one of the most frequently activated signaling
pathways in prostate cancer cells, and loss of the tumor suppressor PTEN and amplification of PIK3CA are the two most
commonly detected mechanisms for the activation of these pathways. Aberrant activation of PI3K/Akt/mTOR has been
implicated not only in the survival and metastasis of prostate cancer cells but also in the development of drug resistance.
As such, selective inactivation of this pathway may provide opportunities to attack prostate cancer from all fronts. However,
while preclinical studies examining specific inhibitors of PI3K or mTOR have yielded promising results, the evidence
from clinical trials is less convincing. Emerging evidence from the analyses of some solid tumors suggests that a
class of dual PI3K/mTOR inhibitors, which bind to and inactivate both PI3K and mTOR, may achieve better anti-cancer
outcomes. In this review, we will summarize the mechanisms of action of these inhibitors, their effectiveness when used
alone or in combination with other chemotherapeutic compounds, and their potential to serve as the next generation therapies
for prostate cancer patients, particularly those who are resistant to the frontline chemotherapeutic drugs.
